118
and − 3.186 kcal/mol, respectively) and van der Waals forces (− 1.496, − 1.432, and
− 1.656 kcal/mol, respectively). The distances between the three hydroxyl groups of
petasiphenol and the hydrophilic residues of Gln76, Arg93, and Arg99 were 1.69,
1.79 and 2.00– 2.04 Å, respectively. The binding energy between the other hydrophilic amino acids (Asp90, Glu92, Ala94, Arg96, Gln102 and Pro104) and petasiphenol is − 11.284 kcal/mol, and the binding energy between the benzene backbone
of petasiphenol and the hydrophobic amino acids (Ile83, Leu95, Leu98, Leu100
and Leu103) was − 15.342 kcal/mol. On the BRCT domain of pol λ, petasiphenol
was smoothly intercalated into the pocket of the loops, and the residues around the
amino acid site consisting of hydrogen bonds (i.e., Gln76, Arg93, and Arg99) appear to be most important for petasiphenol binding [95].
Takeuchi et al. [86] have investigated the structural insights of the interaction
between the pol λ BRCT domain and curcumin derivates. The curcumin is known
as an antichronic inflammatory agent and an anti-oxidative compound. The procedures of BRCT homology modeling, monoacetylcurcumin molecular docking and
binding energy decomposition analysis were carried out in the same way as for
the petasiphenol docking experiment [95]. It was shown that monoacetylcurcumin
binding site on the pol λ surface does not coincide with the petasiphenol binding site
and consists of residues Thr51, Gly52, Gly54, Ala58, Glu59, Glu62, Lys63, Val66,
Val85, Glu87 and Ala113 belonging to β-sheet1 (Thr51, theα-helix-1 (residues
57–69) and two loops (residues 51–56 and 70–75)). The main contribution to the
total binding energy is made by the interaction between curcumin and Lys63—the
energy of this interaction is − 37.93930 kcal/mol (the Coulomb energy is − 29.59488
and the van der Waals energy is − 8.34442 kcal/mol). The energies of interaction
with dicarboxylic amino acids Glu59 and Glu62 are − 7.55664 and − 9.11299 kcal/
mol, respectively [86].
The distances between the three hydroxyl groups of monoacetylcurcumin and the
hydrophilic residues of Glu59, Glu62, and Lys63 are 2.65, 2.74–2.87 and 2.43 Å respectively. The binding energy between the other hydrophilic and neutral amino acids (Thr51 and Glu87) and monoacetylcurcumin is − 7.48746 kcal/mol, the binding
energy between the benzene backbone of monoacetylcurcumin and the hydrophobic
amino acids (Gly52, Gly54, Ala58, Val66, Val85 and Ala113) is – 23.12777 kcal/
mol. On the BRCT domain of pol λ, monoacetylcurcumin is smoothly intercalated
into the pocket of the loops, and the side of the nonacetoxy group on it is just fitted
into pocket of the BRCT domain. The residues around the amino acid site consisting
of a covalent bond (i.e., Cys73) and five hydrogen bonds (i.e. Glu59, Glu62 and,
Lys63) appear to be important for binding to monoacetylcurcumin [86].
Non-nucleotide inhibitors are also able to get bound to the DNA polymerase
active site. So, the above-mentioned gallotannin PGG inhibiting polymerases α, β
and k were docked into the active site on the pol β surface [94]. The docking results show that PGG could form several favorable interactions with the polymerase
catalytic pocket/binding site for the incoming dNTP. The free energy of the binding is predicted to be − 10.26 kcal/mol and the docking runs gave only one possible spatial geometry (Fig. 4.7). In addition, the compound seems to bind in a way
that sterically obstructs two amino acids (Asp192 and Asp196) that are part of the
A. Yu. Nyporko
and − 3.186 kcal/mol, respectively) and van der Waals forces (− 1.496, − 1.432, and
− 1.656 kcal/mol, respectively). The distances between the three hydroxyl groups of
petasiphenol and the hydrophilic residues of Gln76, Arg93, and Arg99 were 1.69,
1.79 and 2.00– 2.04 Å, respectively. The binding energy between the other hydrophilic amino acids (Asp90, Glu92, Ala94, Arg96, Gln102 and Pro104) and petasiphenol is − 11.284 kcal/mol, and the binding energy between the benzene backbone
of petasiphenol and the hydrophobic amino acids (Ile83, Leu95, Leu98, Leu100
and Leu103) was − 15.342 kcal/mol. On the BRCT domain of pol λ, petasiphenol
was smoothly intercalated into the pocket of the loops, and the residues around the
amino acid site consisting of hydrogen bonds (i.e., Gln76, Arg93, and Arg99) appear to be most important for petasiphenol binding [95].
Takeuchi et al. [86] have investigated the structural insights of the interaction
between the pol λ BRCT domain and curcumin derivates. The curcumin is known
as an antichronic inflammatory agent and an anti-oxidative compound. The procedures of BRCT homology modeling, monoacetylcurcumin molecular docking and
binding energy decomposition analysis were carried out in the same way as for
the petasiphenol docking experiment [95]. It was shown that monoacetylcurcumin
binding site on the pol λ surface does not coincide with the petasiphenol binding site
and consists of residues Thr51, Gly52, Gly54, Ala58, Glu59, Glu62, Lys63, Val66,
Val85, Glu87 and Ala113 belonging to β-sheet1 (Thr51, theα-helix-1 (residues
57–69) and two loops (residues 51–56 and 70–75)). The main contribution to the
total binding energy is made by the interaction between curcumin and Lys63—the
energy of this interaction is − 37.93930 kcal/mol (the Coulomb energy is − 29.59488
and the van der Waals energy is − 8.34442 kcal/mol). The energies of interaction
with dicarboxylic amino acids Glu59 and Glu62 are − 7.55664 and − 9.11299 kcal/
mol, respectively [86].
The distances between the three hydroxyl groups of monoacetylcurcumin and the
hydrophilic residues of Glu59, Glu62, and Lys63 are 2.65, 2.74–2.87 and 2.43 Å respectively. The binding energy between the other hydrophilic and neutral amino acids (Thr51 and Glu87) and monoacetylcurcumin is − 7.48746 kcal/mol, the binding
energy between the benzene backbone of monoacetylcurcumin and the hydrophobic
amino acids (Gly52, Gly54, Ala58, Val66, Val85 and Ala113) is – 23.12777 kcal/
mol. On the BRCT domain of pol λ, monoacetylcurcumin is smoothly intercalated
into the pocket of the loops, and the side of the nonacetoxy group on it is just fitted
into pocket of the BRCT domain. The residues around the amino acid site consisting
of a covalent bond (i.e., Cys73) and five hydrogen bonds (i.e. Glu59, Glu62 and,
Lys63) appear to be important for binding to monoacetylcurcumin [86].
Non-nucleotide inhibitors are also able to get bound to the DNA polymerase
active site. So, the above-mentioned gallotannin PGG inhibiting polymerases α, β
and k were docked into the active site on the pol β surface [94]. The docking results show that PGG could form several favorable interactions with the polymerase
catalytic pocket/binding site for the incoming dNTP. The free energy of the binding is predicted to be − 10.26 kcal/mol and the docking runs gave only one possible spatial geometry (Fig. 4.7). In addition, the compound seems to bind in a way
that sterically obstructs two amino acids (Asp192 and Asp196) that are part of the
A. Yu. Nyporko